Levosimendan attenuates multiple organ injury and improves survival in peritonitis-induced septic shock: Studies in a rat model

Critical Care

Volumn 18, Issue 6, 2014, Pages

  Tsao, Cheng Ming ^a,b   Li, Kai Yi ^c   Chen, Shiu Jen ^c,d   Ka, Shuk Man ^c   Liaw, Wen Jinn ^b,c,e   Huang, Hsieh Chou ^f,h   Wu, Chin Chen ^c,g  

^a NATIONAL YANG MING UNIVERSITY   (Taiwan)

^b TRI SERVICE GENERAL HOSPITAL   (Taiwan)

^c NATIONAL DEFENSE MEDICAL CENTER   (Taiwan)

^d Kang Ning Junior College of Medical Care and Management   (Taiwan)

^e TUNGS' TAICHUNG METROHARBOR HOSPITAL   (Taiwan)

^f CHENG HSIN GENERAL HOSPITAL   (Taiwan)

^g TAIPEI MEDICAL UNIVERSITY   (Taiwan)

^h CHENG HSIN REHABILITATION MEDICAL CENTER   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTIINFLAMMATORY AGENT; ASPARTATE AMINOTRANSFERASE; BICARBONATE; CARBON DIOXIDE; CASPASE 3; CREATININE; GLUCOSE; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1BETA; LACTATE DEHYDROGENASE; LEVOSIMENDAN; NITRIC OXIDE; NITRITE; NORADRENALIN; POTASSIUM; SUPEROXIDE; HYDRAZONE DERIVATIVE; PYRIDAZINE DERIVATIVE; SIMENDAN;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ARTERIAL PRESSURE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; AUTOPSY; BICARBONATE BLOOD LEVEL; BLOOD CARBON DIOXIDE TENSION; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DIASTOLIC BLOOD PRESSURE; DISEASE SEVERITY; DRUG EFFECT; GLUCOSE BLOOD LEVEL; HEART RATE; HEMODYNAMICS; HYPERGLYCEMIA; HYPERKALEMIA; HYPOGLYCEMIA; HYPOTENSION; KIDNEY DYSFUNCTION; LACTATE DEHYDROGENASE BLOOD LEVEL; LIVER DYSFUNCTION; LIVER NECROSIS; LUNG EDEMA; LUNG HOMOGENATE; LUNG INFILTRATE; LUNG SEQUESTRATION; MALE; METABOLIC ACIDOSIS; MICROSCOPY; MULTIPLE ORGAN FAILURE; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PERITONITIS; POTASSIUM BLOOD LEVEL; PRESSOR RESPONSE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN INDUCTION; PULSE PRESSURE; RAT; RESPIRATORY ALKALOSIS; SEPTIC SHOCK; SURVIVAL RATE; SYSTOLIC BLOOD PRESSURE; TACHYCARDIA; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; UREA NITROGEN BLOOD LEVEL; ANIMAL; DISEASE MODEL; DRUG EFFECTS; INTRAVENOUS DRUG ADMINISTRATION; MORTALITY; OXIDATIVE STRESS; PATHOLOGY; PHYSIOLOGY; RANDOMIZATION; SHOCK, SEPTIC; TRENDS; WISTAR RAT;

ANIMALS; DISEASE MODELS, ANIMAL; HYDRAZONES; INFUSIONS, INTRAVENOUS; MALE; MULTIPLE ORGAN FAILURE; OXIDATIVE STRESS; PERITONITIS; PYRIDAZINES; RANDOM ALLOCATION; RATS; RATS, WISTAR; SHOCK, SEPTIC; SURVIVAL RATE;

EID: 84926154452     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/s13054-014-0652-4     Document Type: Article

References (44)

1. Ani C, Farshidpanah S, Bellinghausen Stewart A, Nguyen HB: Variations in Organism-Specific Severe Sepsis Mortality in the United States: 1999-2008.Crit Care Med 2014, in press..
2. Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014, 370:1683-1693. 10.1056/NEJMoa1401602, 24635773.
3. Zhou J, Qian C, Zhao M, Yu X, Kang Y, Ma X, Ai Y, Xu Y, Liu D, An Y, Wu D, Sun R, Li S, Hu Z, Cao X, Zhou F, Jiang L, Lin J, Mao E, Qin T, He Z, Zhou L, Du B. Epidemiology and outcome of severe sepsis and septic shock in intensive care units in mainland china. PLoS One 2014, 9:e107181. 10.1371/journal.pone.0107181, 25226033.
4. Spronk PE, Zandstra DF, Ince C. Bench-to-bedside review: sepsis is a disease of the microcirculation. Crit Care 2004, 8:462-468. 10.1186/cc2894, 15566617.
5. Trzeciak S, Cinel I, Phillip Dellinger R, Shapiro NI, Arnold RC, Parrillo JE, Hollenberg SM. Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials. Acad Emerg Med 2008, 15:399-413. 10.1111/j.1553-2712.2008.00109.x, 18439194.
6. Tsao CM, Chen SJ, Shih MC, Lue WM, Tsou MY, Chen A, Liaw WJ, Wu CC. Effects of terbutaline on circulatory failure and organ dysfunction induced by peritonitis in rats. Intensive Care Med 2010, 36:1571-1578. 10.1007/s00134-010-1839-z, 20221745.
7. Haikala H, Kaivola J, Nissinen E, Wall P, Levijoki J, Lindén IB. Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan. J Mol Cell Cardiol 1995, 27:1859-1866. 10.1016/0022-2828(95)90009-8, 8523447.
8. Kivikko M, Lehtonen L. Levosimendan: a new inodilatory drug for the treatment of decompendated heart failure. Curr Pharm Des 2005, 11:435-455. 10.2174/1381612053382043, 15725064.
9. Nieminen MS, Fruhwald S, Heunks LM, Suominen PK, Gordon AC, Kivikko M, Pollesello P. Levosimendan: current data, clinical use and future development. Heart Lung Vessel 2013, 5:227-245. 24364017.
10. Morelli A, Donati A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Cecchini V, Landoni G, Pelaia P, Pietropaoli P, Van Aken H, Teboul JL, Ince C, Westphal M. Levosimendan for resuscitating the microcirculation in patients with septic shocl: a randomized controlled study. Crit Care 2010, 14:R232. 10.1186/cc9387, 21182783.
11. Fries M, Ince C, Rossanit R, Bleilevens C, Bickenbach J, Rex S, Mik EG. Levosimendan but not norepinephrine improves microvascular oxygenation during experimental septic shock. Crit Care Med 2008, 36:1886-1891. 10.1097/CCM.0b013e31817cede9, 18496356.
12. García-Septien J, Lorente JA, Delgado MA, de Paula M, Nin N, Moscoso A, Sánchez-Ferrer A, Perez-Vizcaino F, Esteban A. Levosimendan increases portal blood flow and attenuates intestinal intramucosal acidosis in experimental septic shock. Shock 2010, 34:275-280. 10.1097/SHK.0b013e3181cd8c5b, 19997054.
13. Parissis JT, Adamopoulos S, Antoniades C, Kostakis G, Rigas A, Kyrzopoulos S, Iliodromitis E, Kremastinos D. Effects of levosimendan on circulating pro-inflammatory cytokines and soluble apoptosis mediators in patients with decompensated advanced heart failure. Am J Cardiol 2004, 93:1309-1312. 10.1016/j.amjcard.2004.01.073, 15135713.
14. Boost KA, Hoegl S, Dolfen A, Czerwonka H, Scheiermann P, Zwissler B, Hofstetter C. Inhaled levosimendan reduces mortality and release of proinflammatory mediators in a rat model of experimental ventilator-induced lung injury. Crit Care Med 2008, 36:1873-1879. 10.1097/CCM.0b013e3181743e63, 18496375.
15. Zager RA, Johnson AC, Lund S, Hanson SY, Abrass CK. Levosimendan protects against experimental endotoxemic acute renal failure. Am J Physiol Renal Physiol 2006, 290:F1453-F1462. 10.1152/ajprenal.00485.2005, 16418300.
16. Scheiermann P, Ahluwalia D, Hoegl S, Dolfen A, Revermann M, Zwissler B, Muhl H, Boost KA, Hofstetter C. Effects of intravenous and inhaled levosimendan in severe rodent sepsis. Intensive Care Med 2009, 35:1412-1419. 10.1007/s00134-009-1481-9, 19367398.
17. Shih CC, Chen SJ, Chen A, Wu JY, Liaw WJ, Wu CC. Therapeutic effects of hypertonic saline on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats. Crit Care Med 2008, 36:1864-1872. 10.1097/CCM.0b013e318173f982, 18496380.
18. Yu Z, McNeill JH. Blood pressure and heart rate response to vasoactive agents in conscious diabetic rats. Can J Physiol Pharmacol 1992, 70:1542-1548. 10.1139/y92-221, 1301231.
19. Wu JY, Tsou MY, Chen TH, Chen SJ, Tsao CM, Wu CC. Therapeutic effects of melatonin on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats. J Pineal Res 2008, 45:106-116. 10.1111/j.1600-079X.2008.00567.x, 18298464.
20. Liao MH, Shih CC, Tsao CM, Chen SJ, Wu CC. RhoA/Rho-kinase and nitric oxide in vascular reactivity in rats with endotoxaemia. PLoS One 2013, 8:e56331. 10.1371/journal.pone.0056331, 23457552.
21. Braman RS, Hendrix SA. Nanogram nitrite and nitrate determination in environmental and biological materials by vanadium (III) reduction with chemiluminescence detection. Anal Chem 1989, 61:2715-2718. 10.1021/ac00199a007, 2619057.
22. Tsao CM, Ho ST, Chen A, Wang JJ, Li CY, Tsai SK, Wu CC. Low-dose dexamethasone ameliorates circulatory failure and renal dysfunction in conscious rats with endotoxemia. Shock 2004, 21:484-491. 10.1097/00024382-200405000-00014, 15087827.
23. Yu HP, Lui PW, Hwang TL, Yen CH, Lau YT. Propofol improves endothelial dysfunction and attenuates vascular superoxide production in septic rats. Crit Care Med 2006, 34:453-460. 10.1097/01.CCM.0000198530.68343.21, 16424728.
24. Tsao CM, Ho ST, Liaw WJ, Chen A, Wu CC. Combined effects of propofol and dexamethasone on rats with endotoxemia. Crit Care Med 2008, 36:887-894. 10.1097/CCM.0B013E318165395E, 18431277.
25. Javadi P, Buchman TG, Stromberg PE, Husain KD, Dunne WM, Woolsey CA, Turnbull IR, Hotchkiss RS, Karl IE, Coopersmith CM. High-dose exogenous iron following cecal ligation and puncture increases mortality rate in mice and is associated with an increase in gut epithelial and splenic apoptosis. Crit Care Med 2004, 32:1178-1185. 10.1097/01.CCM.0000124878.02614.4C, 15190970.
26. Gheorghiade M, Teerlink JR, Mebazaa A. Pharmacology of new agents for acute heart failure syndromes. Am J Cardiol 2005, 96:68G-73G. 10.1016/j.amjcard.2005.07.023, 16181825.
27. Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW 3rd, Bland KI, Chaudry IH: Cecal ligation and puncture.Shock 2005, 24:52-57..
28. Wen H. Sepsis induced by cecal ligation and puncture. Methods Mol Biol 2013, 1031:117-124. 10.1007/978-1-62703-481-4_15, 23824895.
29. Zingarelli B, Day BJ, Crapo JD, Salzman AL, Szabó C. The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock. Br J Pharmacol 1997, 120:259-267. 10.1038/sj.bjp.0700872, 9117118.
30. Takakura K, Taniguchi T, Muramatsu I, Takeuchi K, Fukuda S. Modification of alpha1-adrenoceptors by peroxynitrite as a possible mechanism of systemic hypotension in sepsis. Crit Care Med 2002, 30:894-899. 10.1097/00003246-200204000-00030, 11940765.
31. Kimmoun A, Ducrocq N, Levy B. Mechanisms of vascular hyporesponsiveness in septic shock. Curr Vasc Pharmacol 2013, 11:139-149. 23506493.
32. Alvarez S, Evelson PA. Nitric oxide and oxygen metabolism in inflammatory conditions: sepsis and exposition to polluted ambients. Front Biosci 2007, 12:964-974. 10.2741/2117, 17127352.
33. Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 2006, 6:813-822. 10.1038/nri1943, 17039247.
34. Wesche-Soldato DE, Swan RZ, Chung CS, Ayala A. The apoptotic pathway as a therapeutic target in sepsis. Curr Drug Targets 2007, 8:493-500. 10.2174/138945007780362764, 17430119.
35. Boatright KM, Salvesen GS. Mechanisms of caspase activation. Curr Opin Cell Biol 2003, 15:725-731. 10.1016/j.ceb.2003.10.009, 14644197.
36. Plaschke K, Bent F, Wagner S, Zorn M, Kopitz J. In contrast to its anti-inflammatory and anti-apoptotic peripheral effect, levosimendan failed to induce a long-term neuroprotective effect in a rat model of mild septic encephalopathy: a pilot study. Neurosci Lett 2014, 560:117-121. 10.1016/j.neulet.2013.12.021, 24361133.
37. Jaeschke H, Hasegawa T. Role of neutrophils in acute inflammatory liver injury. Liver Int 2006, 26:912-919. 10.1111/j.1478-3231.2006.01327.x, 16953830.
38. Torraco A, Carrozzo R, Piemonte F, Pastore A, Tozzi G, Verrigni D, Assenza M, Orecchioni A, D'Egidio A, Marraffa E, Landoni G, Bertini E, Morelli A. Effects of levosimendan on mitochondrial function in patients with septic shock: A randomized trial. Biochimie 2014, 102:166-173. 10.1016/j.biochi.2014.03.006, 24657218.
39. Mythen MG, Webb AR. Intra-operative gut mucosal hypoperfusion is associated with increased postoperative complications and cost. Intensive Care Med 1994, 20:99-104. 10.1007/BF01707662, 8201106.
40. Pagel PS, Hettrick DA, Warltier DC. Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs. Br J Pharmacol 1996, 119:609-615. 10.1111/j.1476-5381.1996.tb15716.x, 8894186.
41. Schwarte LA, Picker O, Bornstein SR, Fournell A, Scheeren TW. Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs. Crit Care Med 2005, 33:135-142. 10.1097/01.CCM.0000150653.89451.6F, 15644660.
42. Memiş D, Inal MT, Sut N. The effects of levosimendan vs dobutamine added to dopamine on liver functions assessed with noninvasive liver function monitoring in patients with septic shock. J Crit Care 2012, 27:318. e1-6, 21855289.
43. Kopustinskiene DM, Pollesello P, Saris NE. Potassium-specific effects of levosimendan on heart mitochondria. Biochem Pharmacol 2004, 68:807-812. 10.1016/j.bcp.2004.05.018, 15294443.
44. Szilagyi S, Pollesello P, Levijoki J, Kaheinen P, Haikala H, Edes I, Papp Z. The effects of levosimendan and OR-1896 on isolated hearts, myocyte-sized preparations and phosphodiesterase enzymes of the guinea pig. Eur J Pharmacol 2004, 486:67-74. 10.1016/j.ejphar.2003.12.005, 14751410.